ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.

Objectives: The aim of this study was to identify whether the three main primary progressive aphasia (PPA) variants would show differential profiles on measures of visuospatial cognition. We hypothesized that the logopenic variant would have the most difficulty across tasks requiring visuospatial and visual memory abilities. Methods: PPA patients (n=156), diagnosed using current criteria, and controls were tested on a battery of tests tapping different aspects of visuospatial cognition. We compared the groups on an overall visuospatial factor; construction, immediate recall, delayed recall, and executive functioning composites; and on individual tests. Cross-sectional and longitudinal comparisons were made, adjusted for disease severity, age, and education. Results: The logopenic variant had significantly lower scores on the visuospatial factor and the most impaired scores on all composites. The nonfluent variant had significant difficulty on all visuospatial composites except the delayed recall, which differentiated them from the logopenic variant. In contrast, the semantic variants performed poorly only on delayed recall of visual information. The logopenic and nonfluent variants showed decline in figure copying performance over time, whereas in the semantic variant, this skill was remarkably preserved. Conclusions: This extensive examination of performance on visuospatial tasks in the PPA variants solidifies some previous findings, for example, delayed recall of visual stimuli adds value in differential diagnosis between logopenic variant PPA and nonfluent variant PPA variants, and illuminates the possibility of common mechanisms that underlie both linguistic and non-linguistic deficits in the variants. Furthermore, this is the first study that has investigated visuospatial functioning over time in the PPA variants. (JINS, 2018, 24, 259–268)

Executive functioning is widely targeted when human cognition is assessed, but there is little consensus on how it should be operationalized and measured. Recognizing the difficulties associated with establishing standard operational definitions of executive functioning, the National Institute of Neurological Disorders and Stroke entered into a contract with the University of California-San Francisco to develop psychometrically robust executive measurement tools that would be accepted by the neurology clinical trials and clinical research communities. This effort, entitled Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER), resulted in a series of tasks targeting working memory, inhibition, set shifting, fluency, insight, planning, social cognition and behavior. We describe battery conceptualization and development, data collection, scale construction based on item response theory, and lay the foundation for studying the battery's utility and validity for specific assessment and research goals. (JINS, 2013, 19, 1–9)

The following sixteen reference patterns of boride, silicide, nitride and oxide ceramics represent the second group of reference patterns measured at the National Bureau of Standards under the project “High Quality Reference Patterns and Total Digital Powder Patterns of Technologically Important Ceramic Phases”. Included in the sixteen reference patterns are data for two high Tc superconducting oxide phases (CuSr0.2La1.8O4 and Ba2Cu3YO7) plus one related phase (BaCuY2O5). In addition to these new phases, five other patterns represent phases previously not contained in the PDF and eight represent major corrections to data in the file. The general methods of producing these X-ray powder diffraction reference patterns are described in this journal, Vol. 1, No. 1, pg. 40 (1986).

Fifteen reference patterns of boride, silicide, selenide, telluride and oxide ceramics are reported. Included in the 15 reference patterns are data for three oxide phases which are related to high critical temperature (Tc) superconducting materials: BaCuO2, BaCuSm2O5 and BaCuYb2O5. Four other patterns are included which represent phases previously not contained in the PDF. The remaining six are major corrections of data already included in the file. Reference data for phases Ba2CuY3O6.8 and Ba2Y3CuO6 appeared in the special July superconductor issue of the Advanced Ceramic Materials, 1987. The general methods of producing these X-ray powder diffraction reference patterns are described in this journal, Vol. 1(1), 40 (1986).

Samples were mixed with one or two internal standards: silicon (SRM640a), silver, tungsten, or fluorophlogopite (SRM675). Expected 2θ values for these internal standards are specified in the methods described (ibid.). Data were measured with a computer controlled diffractometer. The POWDER-PATTERN system of computer programs was used to locate peak positions, to calibrate the patterns, and to perform variable indexing and least-squares cell refinement. A check on the overall internal consistency of the data was also provided by a computer program.

On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1–11)

Good cognitive performance requires adherence to rules specific to the task at hand. Patients with neurological disease often make rule violation (RV) errors, but the anatomical basis for RV during cognitive testing remains debated. The present study examined the neuroanatomical correlates of RV errors made on tests of executive functioning in 166 subjects diagnosed with neurodegenerative disease or as neurologically healthy. Specifically, RV errors were voxel-wisely correlated with gray matter volume derived from high-definition magnetic resonance images using voxel-based morphometry implemented in SPM2. Latent variable analysis showed that RV errors tapped a unitary construct separate from repetition errors. This analysis was used to generate factor scores to represent what is common among RV errors across tests. The extracted RV factor scores correlated with tissue loss in the lateral middle and inferior frontal gyri and the caudate nucleus bilaterally. When a more stringent control for global cognitive functioning was applied using Mini Mental State Exam scores, only the correlations with the right lateral prefrontal cortex (PFC) remained significant. These data underscore the importance of right lateral PFC in behavioral monitoring and highlight the potential of RV error assessment for identifying patients with damage to this region. (JINS, 2009, 15, 354–364.)

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

Marine paleotemperature is a significant factor in the subsistence productivity of many coastal regions and may be an important factor in the evolution of maritime societies. A California paleotemperature model, spanning 8,000 calendar years, correlates periods of high sea surface temperatures with decreased marine subsistence productivity. A recent case study involving this model identified warming conditions between A.D. 1150 to 1300 as a major cause of subsistence distress for dwellers of the northern Channel Islands. These results are questionable, based on a comparison with data from other sites and periods of high sea temperature. Research at the Little Harbor site, one of the most extensively researched in the Channel Islands, shows that high sea temperature about 5,200 calendar years ago may have introduced warm-water faunas but not starvation conditions. Evidence from other sites occupied during subsequent warming cycles, including the event between A.D. 1150 to 1300, points to similar conclusions. Understanding the effects of long- and short-term ocean temperature cycles, a focus on only a small segment of the Holocene paleotemperature curve, and weak evidence that food abundance was affected by sea temperature are problems that must be overcome before the validity of the paleotemperature model can be accepted.